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  1. Article ; Online: Spontaneous regression of a metastatic carcinoma transmitted by a kidney graft

    Mikhail V. Kiselevskiy / Elena G. Gromova / Nikolay A. Kozlov / Svetlana D. Bezhanova / Irina Zh. Shubina

    Exploration of Targeted Anti-tumor Therapy, Vol 4, Iss 3, Pp 511-

    2023  Volume 518

    Abstract: Transmission of a malignancy from a donor’s organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. ... ...

    Abstract Transmission of a malignancy from a donor’s organ to the recipient of the graft is a rare event, though it is a severe complication that can result in a poor outcome. Usually, immunosuppressive therapy is discontinued and the allograft is removed. However, treatment of patients with the disseminated cancers implies that after the graft removal and cessation of the immunosuppression, radiotherapy, chemotherapy, or immunotherapy with alpha-interferon (INF-α) or interleukin-2 (IL-2) are required. The case report presents a clinical case of a transmitted kidney graft with multiple metastases (MTS) in a 31-year-old woman with the spontaneous regression of the metastatic cancer after transplantectomy and cancellation of the immunosuppressive therapy. Obviously, the determining factor is the recognition of the tumor by the effectors of the antitumor immunity due to the human leukocyte antigen (HLA) mismatch between the donor and the recipient. Therefore, cancellation of the immunosuppressive therapy in cases of transferal of a malignancy with a transplanted organ allows the effectors of the immune system to distinguish the tumor as a foreign tissue and effectively eliminate this neoplasm.
    Keywords cancer ; spontaneous regressions ; kidney graft ; immunosuppressive therapy ; Internal medicine ; RC31-1245
    Subject code 610
    Language English
    Publishing date 2023-06-01T00:00:00Z
    Publisher Open Exploration Publishing Inc.
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  2. Article ; Online: Fucosylated Chondroitin Sulfates with Rare Disaccharide Branches from the Sea Cucumbers Psolus peronii and Holothuria nobilis

    Nadezhda E. Ustyuzhanina / Maria I. Bilan / Natalia Yu. Anisimova / Sofya P. Nikogosova / Andrey S. Dmitrenok / Evgenia A. Tsvetkova / Elena G. Panina / Nadezhda P. Sanamyan / Sergey A. Avilov / Valentin A. Stonik / Mikhail V. Kiselevskiy / Anatolii I. Usov / Nikolay E. Nifantiev

    Pharmaceuticals, Vol 16, Iss 12, p

    Structures and Influence on Hematopoiesis

    2023  Volume 1673

    Abstract: Two fucosylated chondroitin sulfates were isolated from the sea cucumbers Psolus peronii and Holothuria nobilis using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their ... ...

    Abstract Two fucosylated chondroitin sulfates were isolated from the sea cucumbers Psolus peronii and Holothuria nobilis using a conventional extraction procedure in the presence of papain, followed by anion-exchange chromatography on DEAE-Sephacel. Their composition was characterized in terms of quantitative monosaccharide and sulfate content, and structures were mainly elucidated using 1D- and 2D-NMR spectroscopy. As revealed by the data of the NMR spectra, both polysaccharides along with the usual fucosyl branches contained rare disaccharide branches α-D-GalNAc4 S 6 R -(1→2)-α-L-Fuc3 S 4 R → attached to O -3 of the GlcA of the backbone ( R = H or SO 3 − ). The polysaccharides were studied as stimulators of hematopoiesis in vitro using mice bone marrow cells as the model. The studied polysaccharides were shown to be able to directly stimulate the proliferation of various progenitors of myelocytes and megakaryocytes as well as lymphocytes and mesenchymal cells in vitro. Therefore, the new fucosylated chondroitin sulfates can be regarded as prototype structures for the further design of GMP-compatible synthetic analogs for the development of new-generation hematopoiesis stimulators.
    Keywords fucosylated chondroitin sulfate ; Holothuria (Microthele) nobilis ; Psolus peronii ; hematopoiesis ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 540
    Language English
    Publishing date 2023-11-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  3. Article ; Online: Enzymatic Synthesis of 2-Chloropurine Arabinonucleosides with Chiral Amino Acid Amides at the C6 Position and an Evaluation of Antiproliferative Activity In Vitro

    Barbara Z. Eletskaya / Maria Ya. Berzina / Ilya V. Fateev / Alexei L. Kayushin / Elena V. Dorofeeva / Olga I. Lutonina / Ekaterina A. Zorina / Konstantin V. Antonov / Alexander S. Paramonov / Inessa S. Muzyka / Olga S. Zhukova / Mikhail V. Kiselevskiy / Anatoly I. Miroshnikov / Roman S. Esipov / Irina D. Konstantinova

    International Journal of Molecular Sciences, Vol 24, Iss 6223, p

    2023  Volume 6223

    Abstract: A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with ... ...

    Abstract A number of purine arabinosides containing chiral amino acid amides at the C6 position of the purine were synthesized using a transglycosylation reaction with recombinant E. coli nucleoside phosphorylases. Arsenolysis of 2-chloropurine ribosides with chiral amino acid amides at C6 was used for the enzymatic synthesis, and the reaction equilibrium shifted towards the synthesis of arabinonucleosides. The synthesized nucleosides were shown to be resistant to the action of E. coli adenosine deaminase. The antiproliferative activity of the synthesized nucleosides was studied on human acute myeloid leukemia cell line U937. Among all the compounds, the serine derivative exhibited an activity level (IC 50 = 16 μM) close to that of Nelarabine (IC 50 = 3 μM) and was evaluated as active.
    Keywords arabinonucleosides ; nucleoside phosphorylases ; arsenolysis ; adenosine deaminase ; antiproliferative activity ; Biology (General) ; QH301-705.5 ; Chemistry ; QD1-999
    Subject code 540
    Language English
    Publishing date 2023-03-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  4. Article ; Online: Anti-Cancer Potential of Transiently Transfected HER2-Specific Human Mixed CAR-T and NK Cell Populations in Experimental Models

    Irina O. Chikileva / Alexandra V. Bruter / Nadezhda A. Persiyantseva / Maria A. Zamkova / Raimonda Ya. Vlasenko / Yuliya I. Dolzhikova / Irina Zh. Shubina / Fedor V. Donenko / Olga V. Lebedinskaya / Darina V. Sokolova / Vadim S. Pokrovsky / Polina O. Fedorova / Nadezhda E. Ustyuzhanina / Natalia Yu. Anisimova / Nikolay E. Nifantiev / Mikhail V. Kiselevskiy

    Biomedicines, Vol 11, Iss 2563, p

    Initial Studies on Fucosylated Chondroitin Sulfate Usage for Safer Treatment

    2023  Volume 2563

    Abstract: Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T ... ...

    Abstract Human epidermal growth factor receptor 2 (HER2) is overexpressed in numerous cancer cell types. Therapeutic antibodies and chimeric antigen receptors (CARs) against HER2 were developed to treat human tumors. The major limitation of anti-HER2 CAR-T lymphocyte therapy is attributable to the low HER2 expression in a wide range of normal tissues. Thus, side effects are caused by CAR lymphocyte “on-target off-tumor” reactions. We aimed to develop safer HER2-targeting CAR-based therapy. CAR constructs against HER2 tumor-associated antigen (TAA) for transient expression were delivered into target T and natural killer (NK) cells by an effective and safe non-viral transfection method via nucleofection, excluding the risk of mutations associated with viral transduction. Different in vitro end-point and real-time assays of the CAR lymphocyte antitumor cytotoxicity and in vivo human HER2-positive tumor xenograft mice model proved potent cytotoxic activity of the generated CAR-T-NK cells. Our data suggest transient expression of anti-HER2 CARs in plasmid vectors by human lymphocytes as a safer treatment for HER2-positive human cancers. We also conducted preliminary investigations to elucidate if fucosylated chondroitin sulfate may be used as a possible agent to decrease excessive cytokine production without negative impact on the CAR lymphocyte antitumor effect.
    Keywords CAR-lymphocytes ; HER2 ; nucleofection ; immune cancer therapy ; non-viral transfection ; fucosylated chondroitin sulfate ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2023-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  5. Article ; Online: Chondroitin Sulfate and Fucosylated Chondroitin Sulfate as Stimulators of Hematopoiesis in Cyclophosphamide-Induced Mice

    Nadezhda E. Ustyuzhanina / Natalia Yu. Anisimova / Maria I. Bilan / Fedor V. Donenko / Galina E. Morozevich / Dmitriy V. Yashunskiy / Anatolii I. Usov / Nara G. Siminyan / Kirill I. Kirgisov / Svetlana R. Varfolomeeva / Mikhail V. Kiselevskiy / Nikolay E. Nifantiev

    Pharmaceuticals, Vol 14, Iss 1074, p

    2021  Volume 1074

    Abstract: The immunosuppression and inhibition of hematopoiesis are considered to be reasons for the development of complications after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation. Chondroitin sulfate ( CS ), isolated from the ... ...

    Abstract The immunosuppression and inhibition of hematopoiesis are considered to be reasons for the development of complications after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation. Chondroitin sulfate ( CS ), isolated from the fish Salmo salar , and fucosylated chondroitin sulfate ( FCS ), isolated from the sea cucumber Apostichopus japonicus , were studied for their roles as stimulators of hematopoiesis in a model of cyclophosphamide-induced immunosuppression in mice. The recombinant protein r G-CSF was applied as a reference. The studied polysaccharides were shown to stimulate the release of white and red blood cells, as well as platelets from bone marrow in immunosuppressed mice, while r G-CSF was only responsible for the significant increase in the level of leucocytes. The analysis of different populations of leucocytes in blood indicated that r G-CSF mainly stimulated the production of neutrophils, whereas in the cases of the studied saccharides, increases in the levels of monocytes, lymphocytes and neutrophils were observed. The normalization of the level of the pro-inflammatory cytokine IL-6 in the serum and the recovery of cell populations in the spleen were observed in immunosuppressed mice following treatment with the polysaccharides. An increase in the proliferative activity of hematopoietic cells CD34(+)CD45(+) was observed following ex vivo polysaccharide exposure. Further study on related oligosaccharides regarding their potential as promising drugs in the complex prophylaxis and therapy of hematopoiesis inhibition after intensive chemotherapy and allogeneic hematopoietic stem cell transplantation seems to be warranted.
    Keywords graft versus host disease ; granulocyte colony-stimulating factor ; chondroitin sulfate ; fucosylated chondroitin sulfate ; hematopoiesis ; immunosuppression ; Medicine ; R ; Pharmacy and materia medica ; RS1-441
    Subject code 610
    Language English
    Publishing date 2021-10-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  6. Article ; Online: Influence of Modified Fucoidan and Related Sulfated Oligosaccharides on Hematopoiesis in Cyclophosphamide-Induced Mice

    Natalia Yu. Anisimova / Nadezhda E. Ustyuzhanina / Maria I. Bilan / Fedor V. Donenko / Natalia A. Ushakova / Anatolii I. Usov / Mikhail V. Kiselevskiy / Nikolay E. Nifantiev

    Marine Drugs, Vol 16, Iss 9, p

    2018  Volume 333

    Abstract: Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by ... ...

    Abstract Immunosuppression derived after cytostatics application in cancer chemotherapy is considered as an adverse side effect that leads to deterioration of quality of life and risk of infectious diseases. A linear sulfated (1→3)-α-l-fucan M-Fuc prepared by chemical modification of a fucoidan isolated from the brown seaweed Chordaria flagelliformis, along with two structurally related synthetic sulfated oligosaccharides, were studied as stimulators of hematopoiesis on a model of cyclophosphamide immunosuppression in mice. Recombinant granulocyte colony-stimulating factor (r G-CSF), which is currently applied in medicine to treat low blood neutrophils, was used as a reference. Polysaccharide M-Fuc and sulfated difucoside DS did not demonstrate significant effect, while sulfated octasaccharide OS showed higher activity than r G-CSF, causing pronounced neutropoiesis stimulation. In addition, production of erythrocytes and platelets was enhanced after the octasaccharide administration. The assessment of populations of cells in blood and bone marrow of mice revealed the difference in mechanisms of action of OS and r G-CSF.
    Keywords granulocyte colony-stimulating factor ; fucoidan ; synthetic oligosaccharide ; hematopoiesis ; immunosuppression ; cyclophosphamide ; Biology (General) ; QH301-705.5
    Language English
    Publishing date 2018-09-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: Influence of Fucoidans on Hemostatic System

    Mikhail V. Kiselevskiy / Anatolii I. Usov / Marina E. Preobrazhenskaya / Vadim B. Krylov / Albina V. Madzhuga / Oksana V. Somonova / Anna L. Elizarova / Maria I. Bilan / Ksenia A. Zyuzina / Natalia A. Ushakova / Nadezhda E. Ustyuzhanina / Nikolay E. Nifantiev

    Marine Drugs, Vol 11, Iss 7, Pp 2444-

    2013  Volume 2458

    Abstract: Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally ... ...

    Abstract Three structurally different fucoidans from the brown seaweeds Saccharina latissima (SL), Fucus vesiculosus (FV), and Cladosiphon okamuranus (CO), two chemically modified fucoidans with a higher degree of sulfation (SL-S, CO-S), and a synthetic totally sulfated octasaccharide (OS), related to fucoidans, were assessed on anticoagulant and antithrombotic activities in different in vitro experiments. The effects were shown to depend on the structural features of the compounds tested. Native fucoidan SL with a degree of sulfation (DS) of 1.3 was found to be the most active sample, fucoidan FV (DS 0.9) demonstrated moderate activity, while the polysaccharide CO (DS 0.4) was inactive in all performed experiments, even at high concentrations. Additional introduction of sulfate groups into fucoidan SL slightly decreased the anticoagulant effect of SL-S, while sulfation of CO, giving rise to the preparation CO-S, increased the activity dramatically. The high level of anticoagulant activity of polysaccharides SL, SL-S, and CO-S was explained by their ability to form ternary complexes with ATIII-Xa and ATIII-IIa, as well as to bind directly to thrombin. Synthetic per-O-sulfated octasaccharide OS showed moderate anticoagulant effect, determined mainly by the interaction of OS with the factor Xa in the presence of ATIII. Comparable tendencies were observed in the antithrombotic properties of the compounds tested.
    Keywords fucoidan ; anticoagulant ; hemostasis ; heparin ; thrombin ; antithrombin ; factor Xa ; Biology (General) ; QH301-705.5
    Subject code 540
    Language English
    Publishing date 2013-07-01T00:00:00Z
    Publisher MDPI AG
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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